diff --git a/mypy/checkexpr.py b/mypy/checkexpr.py
index 49fc1159856f7..5990619674fe1 100644
--- a/mypy/checkexpr.py
+++ b/mypy/checkexpr.py
@@ -557,6 +557,10 @@ def visit_call_expr_inner(self, e: CallExpr, allow_none_return: bool = False) ->
                     and node
                     and isinstance(node.node, TypeAlias)
                     and not node.node.no_args
+                    and not (
+                        isinstance(target := get_proper_type(node.node.target), TupleType)
+                        and tuple_fallback(target).type.fullname != "builtins.tuple"
+                    )
                     and not (
                         isinstance(union_target := get_proper_type(node.node.target), UnionType)
                         and (
diff --git a/test-data/unit/check-isinstance.test b/test-data/unit/check-isinstance.test
index 0b20d5911151f..e9c9ce3b4827f 100644
--- a/test-data/unit/check-isinstance.test
+++ b/test-data/unit/check-isinstance.test
@@ -1900,6 +1900,21 @@ isinstance(x, It2)  # E: Parameterized generics cannot be used with class or ins
 [builtins fixtures/isinstance.pyi]
 [typing fixtures/typing-full.pyi]
 
+[case testIsinstanceTypeAliasToNamedTuple]
+# flags: --warn-unreachable
+from typing import Any, NamedTuple
+from typing_extensions import TypeAlias
+
+class Foo(NamedTuple):
+    pass
+
+Alias: TypeAlias = Foo
+
+def is_foo(x: Any) -> bool:
+    return isinstance(x, Alias)
+[builtins fixtures/tuple.pyi]
+[typing fixtures/typing-full.pyi]
+
 [case testIssubclassTypeArgs]
 # flags: --warn-unreachable
 from typing import Iterable, TypeVar